Product Code Database
Hemolysins or haemolysins are lipids and proteins that cause lysis of red blood cells by disrupting the cell membrane. Although the lytic activity of some microbe-derived hemolysins on red blood cells may be of great importance for nutrient acquisition, many hemolysins produced by do not cause significant destruction of red blood cells during infection. However, hemolysins are often capable of lysing red blood cells in vitro.
While most hemolysins are protein compounds, some are lipid .
Visualization of hemolysis (UK: haemolysis) of red blood cells in agar plates facilitates the categorization of Streptococcus.
Hemolysin is normally secreted by the bacteria in a water-soluble way. These monomers diffuse to the target cells and are attached to them by specific receivers. After this is done, they oligomerize, creating ring-shaped heptamer complexes.
Hemolysins can be secreted by many different kinds of bacteria such as Staphylococcus aureus, Escherichia coli or Vibrio parahaemolyticus among other pathogens. We can take a look at the bacterium Staphylococcus aureus as a specific example of pore-forming hemolysin production. Staphylococcus aureus is a pathogen that causes many infectious diseases such as pneumonia and sepsis. It produces a ring-shaped complex called a staphylococcal alpha-hemolysin pore. In nature, Staphylococcus aureus secretes alpha-hemolysin monomers that bind to the outer membrane of susceptible cells. Upon binding, the monomers oligomerize to form a water-filled transmembrane channel that facilitates uncontrolled permeation of water, , and small organic molecules. Rapid discharge of vital molecules such as ATP, dissipation of the membrane potential and , and irreversible osmotic swelling leading to the cell wall rupture (lysis) can cause death of the host cell.
This pore consists of seven alpha-hemolysin subunits, which represent the major cytotoxic agent that is freed by this kind of bacterium. These subunits attach to the target cells in the manner described before, and extend the lipid bilayer, forming the . These pores in the cellular membrane will eventually end up causing cell death, since it allows the exchange of monovalent ions that would cause the DNA fragmentation.
The heptamer of α-hemolysin from Staphylococcus aureus has a mushroom-like shape and measures up to 100 Å in diameter and 100 Å in height. A membrane-spanning, solvent-accessible channel runs along the sevenfold axis and ranges from 14 Å to 46 Å in diameter. On the exterior of the 14-strand antiparallel beta-barrel there is a hydrophobic belt approximately 30 Å in width that provides a surface complementary to the nonpolar portion of the lipid bilayer. The interfaces are composed of both salt-links and hydrogen bonds, as well as hydrophobic interactions, and these contacts provide a molecular stability for the heptamer in SDS solutions even up to 65 °C.
As mentioned before, hemolysin is a potential virulence factor produced by , which can put a human's health at risk. Despite causing some severe pathologies, many cases of hemolysis do not suppose a health hazard. But the fact that hemolysins (produced by Pathogen during infections) are combined with other virulence factors may threaten a human's life to a greater extent.
The main consequence of hemolysis is hemolytic anemia, condition that involves the destruction of erythrocytes and their later removal from the bloodstream, earlier than expected in a normal situation. As the bone marrow cannot make erythrocytes fast enough to meet the body's needs, oxygen does not arrive to body tissues properly. As a consequence, some symptoms may appear, such as fatigue, pain, , an enlarged heart or even heart failure, among others.
Depending on the type of hemolysin and the microorganism that produces it, manifestation of symptoms and diseases may differ from one case to the other:
Both aerolysin and alpha-hemolysin are synthesized by extracellular bacteria, which infect specific tissue surfaces.
Hemolysins have proved to be a damaging factor for vital organs, through the activity of Staphylococcus aureus. S. aureus is a dangerous pathogen that may lead cells to necrotizing usually recognized by a massive inflammatory response leading to tissue damage or even tissue destruction. There is a clear example of this: the pneumonia produced by S. aureus. In this case, it has been proven that alpha-hemolysin takes part in inducing necrotic pulmonary injury by the use of the NLRP3 inflammasome, which is responsible for inflammatory processes and of pyroptosis. Pneumonia caused by S. aureus is a common disease in some areas, which is the reason for the many studies in the field of immunology aimed at developing new farmacs to cure easily or prevent this kind of pneumonia. At the moment, apiegnin and beta-cyclodextrin are thought to alleviate S. aureus pneumonia, whereas the antibodies of anti alpha-hemolysin are thought to give protection.
Further findings show that the main virulence factor of S. aureus, the pore-forming toxin α-hemolysin (Hla), is the secreted factor responsible for the activation of an alternative Autophagy. It has been demonstrated that this Autophagy is inhibited by artificially elevating the intracellular levels of cAMP. This process is also mediated by the exchange factors RAPGEF3 and RAP2B.
Another interesting point is that pretreatment of leukocytes with doses of alpha-hemolysin at which nearly 80% of the cells survived decreased the ability of the cells to phagocytize bacteria and particles and to undergo chemotaxis. Premature activation of leukocytes and inhibition of phagocytosis and chemotaxis by alpha-hemolysin, if they occur in vivo, would greatly enhance the survival of an E. coli attack.
Some hemolysins, such as listeriolysin O, allow bacteria to evade the immune system by escaping from . Hemolysins may also mediate bacterial escape from host cells.
When blood cells are being destroyed too fast, extra folic acid and iron supplements may be given or, in case of emergencies, a blood transfusion. In rare cases, the spleen must be removed because it filters blood and removes dead or damaged cells from the bloodstream, worsening the lack of erythrocytes.
|
|
